CN109596844A - 一种检测代谢综合征发病的药物及应用 - Google Patents
一种检测代谢综合征发病的药物及应用 Download PDFInfo
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Abstract
本发明属于医药技术领域，公开了一种检测代谢综合征发病的药物及应用，表明植物甾醇与血压，BMI，空腹血糖，总胆固醇，甘油三酯，LDL‑c水平和hs‑CRP呈负相关(均P<0.01)；植物甾醇与腰围和腰臀比呈负相关，但与吸烟，饮酒，HbA1c无相关性；植物甾醇与代谢综合征呈正相关；糖尿病患者的植物甾醇值低于无罹患者糖尿病。本发明植物甾醇水平与体重指数，腰围，总胆固醇和高敏C反应蛋白呈负相关，但与高密度脂蛋白胆固醇，摄入植物甾醇呈正相关；提出植物甾醇在代谢综合征的过程中起着重要作用。
Description
技术领域
本发明属于医药技术领域，尤其涉及一种检测代谢综合征发病的药物及应用。
背景技术
代谢综合征(MetS)与全因死亡风险增加2倍，心血管死亡风险增加2倍，而2型糖尿病风险增加3倍。MetS被定义为具有以下5种代谢风险因子中的3种或更多种：腹部肥胖，甘油三酯升高，高密度脂蛋白(HDL)胆固醇降低，血压升高和/或空腹血糖升高植物甾醇是结构上与胆固醇高度相似。菜油甾醇和谷甾醇是两种最丰富的植物甾醇，它们不在人体内合成。它们的血浆浓度紧密相关，它们是胆固醇吸收的替代指标。已经证实，中度增加的植物甾醇摄入量也可能降低一般人群的血脂。关于这个问题的流行病学研究一直存在争议。一些研究人员在路德维希港风险和心血管健康(LURIC)研究的参与者中检查了血浆植物甾醇和胆固醇代谢与CAD严重程度的关系。一些研究人员已经证实植物甾醇可以降低血脂。然而，从未研究过MetS与植物甾醇之间的关系。
综上所述，现有技术存在的问题是：尚未探索完全反映代谢综合征特征的缺乏植物甾醇的风险。没有数据显示植物甾醇在代谢综合征患者的情况，且与临床数据有相关性，本发明第一次已知植物甾醇有降脂作用，而植物甾醇的获取主要来源是食物，想通过本研究呼吁代谢综合征患者主动摄入植物甾醇多的食物，做到对植物甾醇的一级预防。
发明内容
针对现有技术存在的问题，本发明提供了一种检测代谢综合征发病的药物及应用。
本发明是这样实现的，一种检测代谢综合征发病的药物，所述代谢综合征发病的药物为物甾醇。
进一步，所述物甾醇与血压，BMI，空腹血糖，总胆固醇，甘油三酯，LDL胆固醇水平和hs-CRP呈负相关。
进一步，所述物甾醇与腰围呈负相关，和腰臀比P<0.01；与年龄，吸烟，饮酒，HbA1c无相关性。
进一步，所述物甾醇植物甾醇与血清高密度脂蛋白胆固醇呈正相关r＝0.15，P＝0.03。
本发明的另一目的在于提供一种所述检测代谢综合征发病的药物在代谢综合征发病中的应用。
本发明的优点及积极效果为：本发明表明植物甾醇与血压，BMI，空腹血糖，总胆固醇，甘油三酯，LDL胆固醇水平和hs-CRP呈负相关(均P<0.01)。植物甾醇与腰围和腰臀比呈负相关(P<0.01)，但与吸烟，饮酒，HbA1c无相关性。此外，植物甾醇与代谢综合征呈正相关(r＝0.15，P＝0.03)。糖尿病患者(HbAlc>6.5％或接受糖尿病药物治疗的患者)(n＝36)的植物甾醇值低于无罹患者糖尿病(n＝64)(259±31vs.367±13，P＝0.0268)。此外，植物甾醇水平与体重指数，腰围，总胆固醇和高敏C反应蛋白呈负相关，但与高密度脂蛋白胆固醇，摄入植物甾醇呈正相关；提出植物甾醇在代谢综合征的过程中起着重要作用。
附图说明
图1是本发明实施提供的物甾醇在代谢综合征发病过程中起重要作用的检测方法流程图。
图2是本发明实施提供的BMI(-)：BMI<24kg/m2BMI(+)：BM≥24kg/m2；HP(-)：<140/90mmHg，HP(+)：≥140/90mmHg；DM(-)：无糖尿病史，此前空腹血糖<6.1mmol/L now.DM(+)：既往有糖尿病史，现在正在使用降糖药或胰岛素.TG(-)：<150mg/dl，TG(+)：≥150mg/dl；TC(-)：<200mg/dl，TC(+)：≥200mg/dl；LDL-C(-)：<100mg/dl，LDL-C(+)：≥100mg/dl，HDL-C(-)：<40mg/dl；HDL-C(+)：≥40mg/dl；Hs-CRP(-)：<0.3mg/dl，Hs-CRP(+)：≥0.3mg/dl。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。
下面结合附图对本发明的应用原理作详细的描述。
如图1所示，本发明实施例提供的物甾醇在代谢综合征发病过程中起重要作用的检测方法包括以下步骤：
S101，收集受试者(n＝100)的数据，这些受试者是包括超重，血脂异常，高血压或葡萄糖耐量降低的代谢综合征，采用回顾性调查连续3天的食物摄入量；
S102，根据2002中国食物成分表计算和比较不同组中植物甾醇的平均摄入量，通过高效液相质谱分析代谢综合征患者体内相关代谢物，并引出潜在可预测代谢综合征的生物标准物。
本发明提供诊断代谢综合征的标准：(1)腹部肥胖(腰围：男性>90cm，女性>85cm)或BMI>30Kg/m2；(2)空腹甘油三酯增加>1.7mmol/L或150mg/dl；(3)LDL-C增加：男性<0.9mmol/L(<35mg/dl)，女性<1.0mmol/L(<1.0mg/d1)；(4)血压升高(>140/90mmHg)或治疗抗高血压；(5)空腹血糖水平高；或葡萄糖耐量降低或胰岛素抵抗或糖尿病；(6)尿白蛋白与肌酸酐的比例：>30mg/g或白蛋白排泄率20g/min；
T2DM或IFG由以下所有的定义确定：(1)空腹血糖水平<100mg/dl；(2)口服降糖药或胰岛素治疗；(3)报告糖尿病史。
下面结合实验对本发明的应用效果作详细的描述。
1、方法
过去常常通过世界卫生组织(WHO)诊断代谢综合征，因为在以下六种成分中存在两种或多种基于T2DM(2型糖尿病)或IFG(葡萄糖耐量降低)的标准：(1)腹部肥胖(腰围：男性>90cm，女性>85cm)或BMI>30Kg/m2；(2)空腹甘油三酯增加>1.7mmol/L或150mg/dl；(3)LDL-C增加：男性<0.9mmol/L(<35mg/dl)，女性<1.0mmol/L(<1.0mg/d1)；(4)血压升高(>140/90mmHg)或治疗抗高血压；(5)空腹血糖水平高；或葡萄糖耐量降低或胰岛素抵抗或糖尿病；(6)尿白蛋白与肌酸酐的比例：>30mg/g或白蛋白排泄率20g/min.T2DM或IFG由以下所有的定义确定：(1)空腹血糖水平<100mg/dl；(2)口服降糖药或胰岛素治疗；(3)报告糖尿病史。采用回顾性方法对所有代谢综合征患者的24小时饮食状况进行膳食状况调查，以便连续三天获得摄入食物。然后根据2002年的中国食物成分表计算日粮中甾醇的平均摄入量。
2、统计分析
除非另有说明，否则所有数据均以比例表示，表示SD或比例。首先，进行卡方检验或t检验以比较研究样本在MetS状态(不存在或存在)方面的特征。然后本发明使用MetS重复分析，因为二分法是edvariable，一个连续变量(数量为MetS标准，以及MetS的每个成分(腰围，甘油三酯，HDL胆固醇水平，血压和血糖等)。计算皮尔森相关系数以评估摄入植物甾醇与临床和实验室测量之间的关联。使用多重逻辑回归分析来计算代谢综合征的存在的调整的奇数比(OR)，并且分析的结果以OR表示，具有95％置信区间(CI)。所有的测试都是双面的。所有统计分析均使用SPSS19.0版(SPSS，Chicago，IL，USA)进行.P值<0.05被认为是显着的。
3、结果
3.1.所有受试者的基线特征和与植物甾醇的相关性分析
如表1所示，受试者的平均BMI，血糖水平，血压和血脂水平略高于标准值，反映了代谢综合征患者的典型特征。通过植物甾醇数据分析，根据BMI，高血压，糖尿病，总胆固醇(TC)和三酰基甘油(TG)指数对代谢综合征进行分组。本发明观察到植物甾醇聚集了所有指标，如BMI，TC，TG和代谢综合征的血压(表1)。
表1-受试者的基线临床和生物化学特征以及与植物甾醇的相关性分析
植物甾醇与血压，BMI，空腹血糖，总胆固醇，甘油三酯，LDL胆固醇水平和hs-CRP呈负相关(均P<0.01)。植物甾醇与腰围和腰臀比呈负相关(P<0.01)，但与吸烟，饮酒，HbA1c无相关性。此外，植物甾醇与血清植物甾醇呈正相关(r＝0.15，P＝0.03)。(表1)
3.2.根据MS的植物甾醇摄入研究受试者的比较
超重(BMI24≥kg/m2)(n＝57)的受试者的摄入植物甾醇水平高于非BMI(BMI<24kg/m2)(n＝43)(423±23vs高血压(≥140/90mmHg)(n＝61)的受试者中有.374±18mg，P＝0.0025)。糖尿病患者(糖化血红蛋白≥6.5％或接受糖尿病治疗)(n＝36)，植物甾醇水平低于非糖尿病患者(n＝64)(259±31vs.367±13mg，P＝0.0268)，以及TG水平高(≥150mg/dl)的受试者)(n＝73)，高于TG正常水平(<150mg/dl)(n＝27)(401±20vs.381±22mg，P＝0.0047)。在LDL胆固醇水平高(LDL-C)(≥100mg/dl)(n＝53)的受试者中，植物甾醇添加值低于LDL-C水平正常(<100mg/dL)的人(n＝47)(345±18vs.396±30mg，P＝0.0034)，TC水平高(≥200mg/dl)的受试者低于正常水平的受试者(392±22vs.405±37)mg，P＝0.0317)。另一方面，HDL胆固醇水平低(HDL-C)(<40mg/dL)(n＝26)的受试者的植物甾醇值高于HDL-C水平正常者(≥40mg/d)dl)(n＝74)(411±33vs.395±19mg，P＝0.0422)。此外，本发明选择高灵敏度C反应蛋白(hs-CRP)作为评估MS的指标。高hs-CRP(≥0.3mg/dl)(n＝60)的受试者的植物甾醇值低于低hs-CRP(<0.3mg/dl)(n＝40)的受试者(336)±22vs.383±27mg，P＝0.0039)。(表2，图2)
表2：根据MS的研究受试者的特征和植物甾醇
3.3.多元逻辑回归分析，反向选择代谢综合征的存在
本发明研究了植物甾醇是否与代谢综合征的存在独立相关。包括年龄，血压，糖尿病，BMI，WC，FBG，TG，TC，LDL-C，HDL-C，hs-CRP和植物甾醇水平作为独立变量。BMI(或每1-SD(95％CI)，1.95(1.14-2.40)；P<0.01)，腰围环境(OR每1-SD(95％CI)，1.45(1.09-2.12)；P<0.01)，TG(或每1-SD(95％CI)，2.97(1.73-3.33)；P<0.01)和hs-CRP(OR＝1-SD(95％CI)，3.45(1.84-4.03)；P<0.01)与代谢综合征风险增加独立相关。HDL-C与代谢综合征的存在呈负相关(OR每1-SD(95％CI)，0.46(0.27-0.80)；P<0.01)。最后，植物甾醇与代谢综合征的存在呈负相关，与年龄无关，血压，糖尿病，BMI，WC，HbA1c，FBG，TG，TC，LDL-C，HDL-C和hs-CRP均为独立变量。(OR1-SD(95％CI)，0.37(0.22-0.64)；P<0.01)(表3)。
表3.多元逻辑回归分析，反向选择代谢综合征的存在
包括年龄，血压，糖尿病，BMI，WC，FBG，TG，TC，LDL-C，HDL-C，hs-CRP和植物甾醇水平作为独立变量。
3.4结果
植物甾醇包含一组仅通过饮食进入哺乳动物体内的甾醇。植物油，坚果和鳄梨中存在相对大量的植物甾醇。本发明的还证实，BMI是代谢综合征患者的高BMI，高血压，高TG，hs-CRP，喜欢食物油，坚果和本发明的调查结果也表明他们的植物甾醇摄入量更高。
植物甾醇具有许多重要的生理功能。已经审查了人类健康和疾病中的作用。同时，大量实验表明，饮食中富含植物甾醇及其饱和衍生物，如甾烷醇，可抑制胆固醇的吸收，使血浆LDL浓度降低10-14％。
植物甾醇的结构与胆固醇非常相似。它们与胆固醇的区别仅在于C24位的额外甲基(菜油甾醇)或乙基(谷甾醇)，或者在C22位的另外的双键(分别为菜子甾醇，豆甾醇)。但是，这个小的结构差异导致哺乳动物中植物甾醇和胆固醇的代谢命运非常不同。胆固醇和植物甾醇都通过Niemann-PickC1-Like1NPC1L1)转运蛋白被肠粘膜细胞内化。胆固醇被转运到内质网，在那里它通过酰基辅酶A：胆固醇O-酰基转移酶2(Acat2)的作用被灭菌，用于掺入乳糜微粒。
近年来，植物甾醇及其衍生物的研究由于其降低胆固醇的作用而引起了本发明的注意，也对循环植物甾醇与CVD风险之间的潜在关联感兴趣。植物甾醇可以经历氧化并形成xyphytolsols，被证明是CVD风险的潜在介质，因为它显示植物甾醇患者血清中约1.4％的循环谷甾醇以其氧化形式存在。然而，植物甾醇是较差的Acat2底物，因此通过异二聚体ATP结合盒(Abc)半转运蛋白g5和g8被转运回腔膜以再分泌到肠腔中。Abcg5和Abcg8存在于肠上皮细胞的顶膜，也在肝脏中表达。最近发现植物甾醇可能参与抗氧化，癌症，并维持正常的神经功能等效果。本发明首次显示植物甾醇与代谢综合征的相关性。如上所示，植物甾醇水平与血压，BMI，空腹血糖，总胆固醇，甘油三酯，LDL胆固醇水平和hs-CRP呈负相关(均P<0.01)。植物甾醇与腰围呈负相关，和腰臀比(P<0.01)，但与年龄，吸烟，饮酒，HbA1c无相关性。此外，植物甾醇与血清高密度脂蛋白胆固醇呈正相关(r＝0.15，P＝0.03)。
在本发明的结果中，首次表明植物甾醇聚集了所有指标，如BMI，TC，TG和代谢综合征的血压。本发明还发现高糖患者的消费量低于代谢综合征患者的正常消费，这可能与严格控制饮食有关，减少食物，特别是油，坚果作为糖尿病的首选治疗方法。本发明的实验也很清楚确认高密度脂蛋白胆固醇和植物甾醇与摄入植物甾醇呈正相关。其他研究证实，植物甾醇的摄入会降低低密度脂蛋白胆固醇(LDL-C)浓度。植物甾醇与代谢综合征的存在呈负相关，与年龄无关，血压，糖尿病，BMI，WC，HbA1c，FBG，TG，TC，LDL-C，HDL-C和hs-CRP作为独立变量被包括在内。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明的保护范围之内。
Claims (5)
1.一种检测代谢综合征发病的药物，其特征在于，所述代谢综合征发病的药物为物甾醇。
2.如权利要求1所述的检测代谢综合征发病的药物，其特征在于，所述物甾醇与血压，BMI，空腹血糖，总胆固醇，甘油三酯，LDL胆固醇水平和hs-CRP呈负相关。
3.如权利要求1所述的检测代谢综合征发病的药物，其特征在于，所述物甾醇与腰围呈负相关，和腰臀比P<0.01；与年龄，吸烟，饮酒，HbA1c无相关性。
4.如权利要求1所述的检测代谢综合征发病的药物，其特征在于，所述物甾醇植物甾醇与血清高密度脂蛋白胆固醇呈正相关r＝0.15，P＝0.03。
5.一种如权利要求1所述检测代谢综合征发病的药物在代谢综合征发病中的应用。
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| CN104411319A (zh) * | 2012-07-23 | 2015-03-11 | 雀巢产品技术援助有限公司 | 山楂和植物甾醇类及其对代谢性疾病的作用 |
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| US5965449A (en) * | 1996-07-03 | 1999-10-12 | Forbes Medi-Tech, Inc. | Method of assessing risk for cardiovascular disease and other disorders and phytosterol-based compositions useful in preventing and treating cardiovascular disease and other disorders |
| WO2004105770A1 (en) * | 2003-05-31 | 2004-12-09 | Forbes Medi-Tech Inc. | Composition comprising one or more phytosterols and/or phytostanols and glucomannan and uses of the composition in treating lipid disorders in individuals with and without type ii diabetes |
| CN104411319A (zh) * | 2012-07-23 | 2015-03-11 | 雀巢产品技术援助有限公司 | 山楂和植物甾醇类及其对代谢性疾病的作用 |
| CN104126801A (zh) * | 2014-08-12 | 2014-11-05 | 中粮天科生物工程(天津)有限公司 | 一种含甾醇的降血脂组合物 |
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| WO2024046160A1 (zh) * | 2022-09-02 | 2024-03-07 | 广东药科大学 | 一种综合评价糖脂代谢水平的系统及其应用 |
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